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- Burisch, Johan, et al.
(författare)
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Disease course of inflammatory bowel disease unclassified in a European population-based inception cohort : an Epi-IBD study
- 2019
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Ingår i: Journal of Gastroenterology and Hepatology. - : John Wiley & Sons. - 0815-9319 .- 1440-1746. ; 34:6, s. 996-1003
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following five years.METHODS: The Epi-IBD study is a prospective population-based cohort of 1,289 IBD patients diagnosed in centres across Europe. Clinical data were captured prospectively throughout the follow-up period.RESULTS: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n=20, 71%) or CD (n=8, 29%) after a median of six months (IQR: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n=6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n=107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU.CONCLUSIONS: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after five years of follow-up. One in four patients with IBDU eventually were classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.
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| 2. |
- Burisch, Johan, et al.
(författare)
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Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study
- 2019
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 13:2, s. 198-208
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.
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| 3. |
- Isidor, Marie S., et al.
(författare)
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An siRNA-based method for efficient silencing of gene expression in mature brown adipocytes
- 2016
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Ingår i: Adipocyte. - : Informa UK Limited. - 2162-3945 .- 2162-397X. ; 5:2, s. 175-185
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Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue is a promising therapeutic target for opposing obesity, glucose intolerance and insulin resistance. The ability to modulate gene expression in mature brown adipocytes is important to understand brown adipocyte function and delineate novel regulatory mechanisms of non-shivering thermogenesis. The aim of this study was to optimize a lipofection-based small interfering RNA (siRNA) transfection protocol for efficient silencing of gene expression in mature brown adipocytes. We determined that a critical parameter was to deliver the siRNA to mature adipocytes by reverse transfection, i.e. transfection of non-adherent cells. Using this protocol, we effectively knocked down both high-and low-abundance transcripts in a model of mature brown adipocytes (WT-1) as well as in primary mature mouse brown adipocytes. A functional consequence of the knockdown was confirmed by an attenuated increase in uncoupled respiration (thermogenesis) in response to beta-adrenergic stimulation of mature WT-1 brown adipocytes transfected with uncoupling protein 1 siRNA. Efficient gene silencing was also obtained in various mouse and human white adipocyte models (3T3-L1, primary mouse white adipocytes, hMADS) with the ability to undergo browning. In summary, we report an easy and versatile reverse siRNA transfection protocol to achieve specific silencing of gene expression in various models of mature brown and browning-competent white adipocytes, including primary cells.
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| 4. |
- Isidor, Marie S., et al.
(författare)
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Pyruvate kinase M2 represses thermogenic gene expression in brown adipocytes
- 2020
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 594:7, s. 1218-1225
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Tidskriftsartikel (refereegranskat)abstract
- Utilizing the thermogenic capacity of brown adipose tissue is a potential anti-obesity strategy; therefore, the mechanisms controlling expression of thermogenesis-related genes are of interest. Pyruvate kinase (PK) catalyzes the last step of glycolysis and exists as four isoenzymes: PK, liver, PK, red blood cell, PK, muscle (PKM1 and PKM2). PKM2 has both glycolytic and nuclear functions. Here, we report that PKM2 is enriched in brown adipose compared with white adipose tissue. Specific knockdown of PKM2 in mature brown adipocytes demonstrates that silencing of PKM2 does not lead to a decrease in PK activity, but causes a robust upregulation of thermogenic uncoupling protein 1 (Ucp1) and fibroblast growth factor 21 (Fgf21) gene expression. This increase is not mediated by any of the known mechanisms for PKM2-regulated gene expression, thus implying the existence of a novel mechanism for PKM2-dependent effects on gene expression.
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